amc4air

E pur si muove

[amc4air @amc4air]

@artemg314 I don’t understand the link between your preclinical molecule assessment and phase 3 forecasting, there are many other factors involved in between, can you please elaborate? Also, what type of phase 3 indications are you looking at?

[Martin Borch Jensen @MartinBJensen]

Learning biotech part 2:
Once you understand process of finding drugs, you should study the incentives that drive decisions.

Why does someone choose to launch the 200th EGFR program? Inevitably there's a set of incentives, and often data-driven risk analysis, motivating these seemingly silly decisions.
While new biotechs often challenge existing assumptions, understanding Chesterton's fence is the smartest way to decide where and why you deviate.

I would start by reading AstraZeneca's retrospective on why their programs won or lost:
“Lessons learned from the fate of AstraZeneca’s drug pipeline: a five-dimensional framework.” https://t.co/8fPq5HAeNu
The '5Rs' they identified are a good representation of the risks pharma prioritizes: right target, right tissue, right safety, right patient, and right commercial potential.

YC tells their companies to talk to users. But who is the 'user' for biotech?
- Ultimately, we make medicines for patients to enjoy healthy lives.
- The FDA judges whether it works.
- But doctors decide what to prescribe.
- And insurance and medicare actually pay for the treatment.
This makes the situation more confusing for new biotechs. But your product needs to work for all four of those user.
(even if you plan to sell to pharma before approval, they have the same users, so you just have one more user to please)

I recommend the book 📚 "Her-2" about Genentech's mega-successful drug Herceptin, which includes decisions about which diseases and trials they tried it for first. If those decisions had been wrong, the drug might have died.

I'd also recommend (any and all) episodes of 🎧 "Hard Drugs" from @salonium and @JacobTref, especially for examples where the science incentives are stronger than financial ones.
https://t.co/uVXhWUtv8U

After that, try deconstructing decisions you see in the news, like Genentech choosing to exit cancer immunology two years ago or everyone buying 'radiopharmaceutical' biotechs. What got derisked, or saw added risk?

One source of 'irrational behavior' might be classic short-term performance goals among executives at public companies. At any given time, pharma's revenue come from a small number of patent-protected drugs. When patents expire on a top product revenue plummets, so you often see acquisitions of mature companies that might get a new big approval before the cliff.
Basics of patent cliffs here: https://t.co/HjdNuTh6fw
and this episode of @alexkesin and Matthew Pech's 🎧 Approved goes deep on that drug, including at ~90m how Merck sought to protect its profits: https://t.co/mvnZQWcUbR

Ultimately, incentives all come back to 1) a desire to improve humanity's conditions by scientists who go into biomedicine, and 2) free market competition.
When you see something that seems cool (like PCSK9 gene therapy) but isn't super hot, check the incentive stack to understand why (in this case, strong competition with lower risk).
And when you see an opportunity nobody is filling, at least find out why.

More good content on this topic includes:
@alexkesin’s ✍️ “Pharmacopoeia” broadly covers how biopharma behaves, for example in “Pharma Is Hollywood, Roughly”:
https://t.co/8Vt3nWzNBH

@ElliotHershberg’s ✍️ “The Century of Biology” has a series on platform companies, like BridgeBio, that dissects incentives:
https://t.co/3NdCYjqT6n

Finally, 📚 “The Great American Drug Deal” by @PeterKolchinsky is relevant as big picture context on how healthcare works and how the medicines it pays for flows back into the next generation of drugs. You can also get the short version on this website: https://t.co/CZ9kzQLhKG

[Evan Tindell @evantindell]

Get the knives out because it's time to discuss some ridiculously valued stocks in today's market.

We are short some but not all of these so do your own work.

What did I miss????

$SPCX I mean obviously

$TSLA -- Do you understand you are paying one TRILLION dollars for options on cybercab and robots?

$ASTS -- $20b market for a space cell tower company with zero subscribers that will do less than $200m of revenue this year. Street estimates had been $500m for 2026e revenue in early 2025. They'll burn $1.7b this year, and their main competition, $SPCX, is light years (see what I did there) ahead in terms of commercial uptake.

$WDFC -- 5x sales and 40x earnings for a mid-single digit growing lubricants company? Give me a break.

$NBIS -- GPU data center or a they like to call it, "AI factory" company. The bull case at current valuations of $56b need them to generate 70% EBITDA margins ($CRWV is at low 60s and declining) on like $100b of revenue in 2030 unless GPUs don't actually depreciate . Just have to hope everything goes absolutely perfectly and that you can fund the whole thing relatively cheaply and MAYBE it can work. I doubt it. Meanwhile they trade at 15x FORWARD revenue.

$INTC -- Been getting their lunch eaten in data center CPU market share for several quarters now, but apparently having the US govt as a shareholder and increased demand for CPUs to handle agentic workflows is worth $400b of market cap. Much of the increase in CPU revenue 2026-2030 will go to NVDA-attached ARM CPUs or AMD. Meanwhile the stock trades at 100x forward earnings and negative FCF.

$UEC - North American Uranium company trading at a mere 200x 2026e sales. Awesome.

$WMT -- 40x earnings for mid-single digit grower. 🤓

$OKLO / $SMR Many billions in market cap. Very little prospect of generating profits in the next 5 years, if ever.

Anything Quantum is a heaping pile of trash $IONQ, $QBTS etc.

[amc4air @amc4air]

Pari Passu Newsletter. Really interesting stuff.

[Restructuring__ @Restructuring__]

First Brands will go down as one of the most brutal bankruptcies of all time

Diameter, a leading credit hedge fund, just shared how they incurred their biggest loss in history, burning hundreds of millions

Read below how the smartest investors in the world got their faces ripped off

Get the Full Letter below ⬇️

1/n The Set-Up

[Sophocles Sophocleous, CFA @FatAlpha]

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Recordings available post-event.

Included: FREE BONUSES WORTH €1,000+
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Feedback from in-person events:
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Don't Miss Out.
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[Liger Cub @realLigerCub]

IDEA GENERATION (5/N): INVESTMENT WRITE-UP PLATFORMS

In 1999, Joel Greenblatt and John Petry founded Value Investors Club (VIC) as a forum for high-quality idea generation. Prior to VIC gaining recognition, investors resorted to noisy platforms like Silicon Investor (SI), where notable users such as Dan Loeb (@DanielSLoeb1), under the alias Mr. Pink (https://t.co/QV8H1hdmu7), and Michael Burry (https://t.co/jmgNd3uxu7) were active.

Today, VIC has ~500 active members (originally capped at 250), with an acceptance rate of only about 1 in 15 applications. Faced with criticisms of being a closed community and concerns about diminishing quality, alternative platforms emerged, such as SumZero. Furthermore, two new VIC-inspired websites have recently been established, namely Savant Investors and MyBuyside, but their quality will be assessed as time unfolds.

Beyond the aforementioned platforms, MicroCapClub stands out as a respected hub for experienced microcap investors. I’ve attached their webinar “A Beginner’s Guide to Researching Microcap Stocks”, a valuable resource offering plenty of useful information. Additionally, Seeking Alpha serves, among others, as a platform where independent contributors share write-ups, despite the presence of numerous low-quality articles.

To sum up, the following are all the investment write-up platforms mentioned above:

• Value Investors Club (VIC): https://t.co/x3qzbQORIS
• SumZero (@SumZero): https://t.co/abwyAq3V6Q
• MicroCapClub (@MicroCapClub, @iancassel): https://t.co/jhyLvCAzho
• Seeking Alpha (@SeekingAlpha): https://t.co/GdaQtZwjbX
• Savant Investors (@savantinvestors): https://t.co/iAqM7F9SOx
• MyBuyside (@MyBuyside): https://t.co/FeLWxij05Z

Finally, find below some well-established money managers and their VIC accts (h/t @TaoValue):

• Anthony Bozza – hawkeye901: https://t.co/fsdmxoWnJc
• Christopher Mittleman – mimval: https://t.co/OQxYhU7KPr
• Connor Leonard – CFL41: https://t.co/DRDvslaFr9
• Daniel Sundheim – sunny329: https://t.co/mALMCVKo1H
• Edgar Wachenheim – lordbeaverbrook: https://t.co/uwy6sFgaUN
• Gary Claar – gary9: https://t.co/brLNNJlfGz
• Harris Kupperman – hkup881: https://t.co/oUemmyUf8W
• Mohnish Pabrai – nish697: https://t.co/anVhZREXUX
• Michel Burry – michael99: https://t.co/VHaCtiLo83
• Nathaniel August – nha855: https://t.co/KbhQYPzzab
• Norbert Lou - charlie479: https://t.co/5VqJ0LxKud
• Vitaliy Katsenelson – murman: https://t.co/BEkZkytZJm
• Whitney Tilson – wrt233: https://t.co/6VKkJPLMmV

Any additions?

[Frederik Gieschen @FrederikNeckar]

Sam Zell: no surprises.

"As a risk-taker, my greatest fear is not having information that might protect me from making a mistake. The only way I can do that is to create an atmosphere where there are no silos. I tell people “No surprises” and I mean it."

[Compounding Quality @QCompounding]

Great stock selection process by Francois Rochon:

[Tuike Souza @TuikeSouza]

Esta obra ha sido realizada en la Plaça del Baluard, dentro del proyecto Reus Urban Art,… https://t.co/77KBkRQLpH

[Tuike Souza @TuikeSouza]

Esta obra ha sido realizada en la Plaça del Baluard, dentro del proyecto Reus Urban Art,… https://t.co/uTfdNPbq0Z

[amc4air @amc4air]

@jonostrower Maybe you forgot something... fuel consumption and maintenance costs? Good try though

[✈Paul Job✈ 🇿🇦📷 @pauljob]

#wednesdaywisdom You decide what you want to do in life, be afraid and run away or stand your ground and take your life's photo, you decide.

[TITZINA @Titzina]

a una semana de viajar a Lationamerica #titzina #distanciasieteminutos. Nos vemos en Uruguay y Brasil.

[amc4air @amc4air]

@DusanKranjc amazing solo!! #2cellos

[amc4air @amc4air]

@stjepanhauser @lukasulic welcome to #Mallorca!! Just 15 min late but we'll enjoy it!!

[Paul Craven @CravenPartners]

Thought for the day for @Gerald_Ashley and @rorysutherland

[amc4air @amc4air]

And which plane is this, an @Airbus or a @Boeing?

[amc4air @amc4air]

Which #airport is this? #beer #art

[Robert J Shiller @RobertJShiller]

Listen Carefully for Hints of the Next Global Recession https://t.co/A424n9lXKl via @UpshotNYT

[Jon Ostrower @jonostrower]

The most complex machines ever mass produced (don’t even look at me tech reporters) and we get these colors. Meh. https://t.co/kFE8J6k9PJ